The etiology for diabetes is known to be mostly owing to disturbances of insulin secretion in the pancreatic .beta.-cells. Consequently, elucidation of the molecular mechanism of insulin secretion is expected to play an important role in the clarification of causes for diabetes and the development of therapeutic agents against diabetes, but no detail has yet been made known on such molecular mechanism.
It has been made clear that the ATP-sensitive potassium channel (K.sub.ATP channel) being present on the cellular membrane plays a leading role in the cellular functions such as secretions and muscular contraction by conjugating the state of metabolism in the cells with the membrane potential. For example, the K.sub.ATP channel has been confirmed to be present in the cardiac muscle in 1983 Noma, A., Nature 305:147 (1983)! the pancreatic .beta.-cell Cook; D. L. et al., Nature 311:271 (1984), Misler, S. et al., Proc. Natl. Acad. Sci. U.S.A. 83:7119 (1986)!, pituitary Bernardi, H. et al., Proc. Natl. Acad. Sci U.S.A., 90:1340 (1993)!. skeletal muscle Spruce, A. E., et al., Nature, 316: 736 (1985)!, etc.
In the pancreatic .beta.-cells, particularly, ATP produced by the metabolism of glucose brings about ion inflow from the calcium channel by closing the K.sub.ATP channel to cause depolarization, resulting in secretion of insulin. As is evident from this, the K.sub.ATP channel plays a leading role in regulating the secretion of insulin.
The K.sub.ATP channel belongs to a potassium channel family exhibiting electrophysiologically inward rectification, whereby the potassium channel family exhibiting inward rectification is classified into the five subfamilies (ROMK1, IRK1, GIRK1 and cK.sub.ATP -1 and uK.sub.ATP -1) on the basis of the degree of amino acid sequence identity.
Nevertheless, there has not been clarified the molecular architecture for the K.sub.ATP channel in the pancreatic .beta.-cells. uK.sub.ATP -1 that has been found by the present inventors to be ubiquitous in various tissues is expressed in the normal tissues including the pancreatic .beta.-cells but not expressed in the insulin-secreting cell line.
In view of the above, the present inventors searched into a potassium channel which is to be expressed specifically in the pancreatic .beta.-cells and insulin-secreting cell line.
The novel ATP-sensitive potassium channel that is expressed specifically in the pancreatic .beta.-cells has not yet been clarified for its detailed protein structure, while no information has been disclosed on the formation of complexes with other proteins, for example, the novel potassium channel (uK.sub.ATP -1) being ubiquitous in tissues and sulfonylurea binding protein.